C. difficile is a Gram-negative, spore forming anaerobic bacterium that can reside asymptomatically in the intestinal tract of humans. Depletion of other intestinal flora, for example by antibiotic and chemotherapeutic treatment, creates an ecological niche which allows C. difficile spores to germinate in the colon, resulting in serious intestinal disease [1]. Antibiotic treatment can therefore transform this normally harmless micro-organism into the causative agent of a spectrum of intestinal diseases, an outcome that is particularly prevalent in hospitalised patients.
C. difficile is the predominant pathogen of nosocomial intestinal infections [2, 3] and causes approximately 20% of the cases of antibiotic-associated diarrhoea, up to 75% of the cases of antibiotic-associated colitis, and nearly all cases of pseudomembranous colitis [4]. Host factors such as advancing age, pre-existing severe illness and weakened immune defences predispose individuals to symptomatic infection [1]. Such C. difficile-associated disease (CDAD) usually occurs in intensive care units, particularly affecting patients over 60 years of age.
Treatment of CDAD typically involves the cessation of the offending antibiotic, initiation of oral metronidazole or vancomycin therapy and fluid replacement. However, the emergence of antibiotic-resistant enteropathogens has led to concerns over the use of antibiotics to treat CDAD. Moreover, up to 20% of patients relapse within 1-2 weeks of completing a course of antibiotics and the risk of relapse increases markedly with each additional relapse [5,6]. It is also reported that over 50% of the relapse incidents are due to a re-infection with a different C. difficile strain, rather than recurrence of the primary infection [7]. Preventive measures are based on patient isolation, implementation of hand hygiene and contact precaution, which have had variable and often limited success.
There is at present, no effective vaccine against CDAD. It is an object of the invention to provide compositions which are effective in raising immune responses against C. difficile for use in the development of vaccines for preventing and/or treating C. difficile associated diseases.